During the development of the central nervous system (CNS), cells in the ventricular zone of the neural tube generate an enormous number of different types of neurons and glia. An understanding of the extracellular signals that control the processes of neurogenesis and neuronal differentiation is necessary for any future attempts at reconstruction and regeneration of damaged CNS and for understanding the basis for neoplastic transformation and the action of teratogenic agents. The model system used in this research program is the mammalian retina. The factors that regulate proliferation and differentiation have been studied in a dissociated culture system of retinal progenitor cells and, in the next period, the role of these factors will be assessed in vivo. The hypothesis that the epidermal growht factor (EGF) receptor tyrosine kinase controls neuronal number will be tested by studying mutant mice with disruptions in EGF receptor function. The hypothesis that retinoids are necessary for rod photoreceptor differentiation will be tested by determining the distribution of retinoid and their receptors in the developing retina and experimentally perturbing the levels of retinoids and their receptors in vivo.